This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This trial will test the safety and efficacy of sirolimus Rapamycin in patients with lymphangioleiomyomatosis- LAM. Two hundred and forty patients will be randomized to placebo or sirolimus groups, treated for one year and followed off of drug or placebo for one additional year. The primary outcome will be change in forced expiratory volume in one second slope-FEV1 slope over twelve months. The analysis will be based on an 'intention to treat'design. Interim analyses will occur when 100 patients reach the one year point. The final analysis, which will assess the durability of response, will occur at 24 months. Secondary outcome measures will include forced vital capacity, residual volume, diffusing capacity, six minute walk, all cause mortality and questionnaire based assessments of dyspnea, fatigue and depression.